KR20040018538A - Reductive cleavage of the exocyclic ester of UK-2A or its derivatives and products formed therefrom - Google Patents
Reductive cleavage of the exocyclic ester of UK-2A or its derivatives and products formed therefrom Download PDFInfo
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- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
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Abstract
(a)환원제의 존재하에, (b)비양성자성 용매의 존재하에 및 (c)반응 조건하에, 화합물 GF-I을 환원제와 반응시켜 화합물 GF-II를 형성함을 포함하는 방법이 제공된다.There is provided a method comprising reacting compound GF-I with a reducing agent in the presence of (a) in the presence of a reducing agent, (b) in the presence of an aprotic solvent and (c) in reaction conditions.
반응식 GR-IScheme GR-I
위의 반응식 GR-I에서,In Scheme GR-I above,
Y는 H, 벤질, 치환된 벤질, CH2OC1-8알킬, CH2OC3-8사이클로알킬, 알릴, 테트라하이드로피라닐, 테트라하이드로푸라닐, 치환된 테트라하이드로피라닐, 치환된 테트라하이드로푸라닐, Si(C1-4알킬)3및 Si(Ph)x(C1-4알킬)3-x(여기서, x는 1, 2 또는 3이다)로 이루어진 그룹으로부터 선택된다.Y is H, benzyl, substituted benzyl, CH 2 OC 1-8 alkyl, CH 2 OC 3-8 cycloalkyl, allyl, tetrahydropyranyl, tetrahydrofuranyl, substituted tetrahydropyranyl, substituted tetrahydro Furanyl, Si (C 1-4 alkyl) 3 and Si (Ph) x (C 1-4 alkyl) 3-x , where x is 1, 2 or 3;
또한, 이로부터 생성된 신규한 화합물이 제공된다.Also provided are novel compounds produced therefrom.
Description
발명의 분야Field of invention
본 발명은 화합물로부터 에스테르를 분해시키기 위해 사용되는 방법의 분야, 살진균제로서 사용될 수 있는 화합물의 분야, 및 또한 살진균제로서 사용될 수 있는 화합물을 생성하기 위해 사용될 수 있는 화합물의 분야에 관한 것이다.The present invention relates to the field of methods used to decompose esters from compounds, to the field of compounds that can be used as fungicides, and also to the field of compounds that can be used to produce compounds that can be used as fungicides.
발명의 배경Background of the Invention
UK-2A는 다음의 화학식을 갖는 천연 생성물이다.UK-2A is a natural product having the formula:
UK-2A는 문헌[참조: M. Ueki, et al. J. Antibiot. 1996, 49, 639]에 기술되어 있다. 당해 화합물은 이를 각종 분야에서 유용하게 만드는 특성을 가지며, 일반적으로 이는 살진균제 분야에서 효능을 갖는 화합물을 제조하기 위한 출발점으로서 연구되고 있다.UK-2A is described in M. Ueki, et al. J. Antibiot. 1996, 49, 639. The compounds have the properties that make them useful in a variety of fields and are generally studied as starting points for preparing compounds having efficacy in the field of fungicides.
발명의 요약Summary of the Invention
본 발명의 목적은 UK-2A의 엑소사이클릭 에스테르 또는 이의 유도체를 환원성 분해시키고 신규한 화합물을 생성하는 방법을 제공하는 것으로, 이들은 생물학적 활성 물질의 합성에 있어서 유용한 중간체이다.It is an object of the present invention to provide a method for reductively digesting exocyclic esters of UK-2A or derivatives thereof and producing novel compounds, which are useful intermediates in the synthesis of biologically active substances.
본 발명에 따라서, 특정한 방법이 제공된다. 상기 방법은 화합물 GF-I을 환원제와 반응시켜 화합물 GF-II를 형성함을 포함한다. 또한, 이로부터 생성된 신규한 화합물이 청구된다.In accordance with the present invention, certain methods are provided. The method comprises reacting compound GF-I with a reducing agent to form compound GF-II. Also claimed are new compounds produced therefrom.
당해 출원을 위해, 다음의 용어들은 다음의 의미를 갖는다. 용어 "Ph"는 페닐을 의미한다. 용어 "Me"는 메틸을 의미한다. 용어 "EtOAc"는 에틸 아세테이트를 의미한다. 용어 "ppm"은 백만분의 1부를 의미한다. 용어 "psia"는 평방 인치당 파운드를 의미한다. 용어 "m.p."는 융점을 의미한다. 본 문헌에 걸쳐서, 달리 언급하지 않는 한, 온도는 모두 섭씨(℃)로 주어지고, 백분율은 모두 중량%이고, 융점은 모두 보정되지 않는다.For the purposes of this application, the following terms have the following meanings. The term "Ph" means phenyl. The term "Me" means methyl. The term "EtOAc" means ethyl acetate. The term "ppm" means parts per million. The term "psia" means pounds per square inch. The term "m.p." means melting point. Throughout this document, unless stated otherwise, temperatures are all given in degrees Celsius (° C.), percentages are all weight percent, and melting points are not all corrected.
발명의 상세한 설명Detailed description of the invention
위의 반응식 GR-I에서,In Scheme GR-I above,
Y는 H, 벤질, 치환된 벤질, CH2OC1-8알킬, CH2OC3-8사이클로알킬, 알릴, 테트라하이드로피라닐, 테트라하이드로푸라닐, 치환된 테트라하이드로피라닐, 치환된 테트라하이드로푸라닐, Si(C1-4알킬)3및 Si(Ph)x(C1-4알킬)3-x(여기서, x는 1, 2 또는 3이다)로 이루어진 그룹으로부터 선택된다.Y is H, benzyl, substituted benzyl, CH 2 OC 1-8 alkyl, CH 2 OC 3-8 cycloalkyl, allyl, tetrahydropyranyl, tetrahydrofuranyl, substituted tetrahydropyranyl, substituted tetrahydro Furanyl, Si (C 1-4 alkyl) 3 and Si (Ph) x (C 1-4 alkyl) 3-x , where x is 1, 2 or 3;
용어 "치환된 벤질"은 하나 이상의 치환체를 갖는 벤질 그룹을 의미한다. 치환된 벤질의 환 위의 치환체는 "환 치환체"라고 불린다. 환 치환체는 할로(F, Cl 및 Br), C1-8알콕시, C2-8알켄옥시, C5-8사이클로알콕시 및 페닐옥시로 이루어진 그룹으로부터 선택된다. 치환된 벤질의 메틸렌 탄소 위의 치환체는 "메틸렌 치환체"로 불린다. 메틸렌 치환체는 C1-3알킬이다. 하나 이상의 수소를 갖는 환과 메틸렌 치환체 각각은 할로겐(F, Cl 및 Br)으로 치환된 이러한 수소를 하나 이상 가질 수 있다.The term "substituted benzyl" means a benzyl group having one or more substituents. Substituents on a ring of substituted benzyl are called "ring substituents". Ring substituents are selected from the group consisting of halo (F, Cl and Br), C 1-8 alkoxy, C 2-8 alkenoxy, C 5-8 cycloalkoxy and phenyloxy. Substituents on the methylene carbon of substituted benzyl are called "methylene substituents". The methylene substituent is C 1-3 alkyl. Each ring and one methylene substituent having at least one hydrogen may have one or more such hydrogens substituted with halogen (F, Cl and Br).
용어 "치환된 테트라하이드로피라닐" 및 "치환된 테트라하이드로푸라닐"은 할로(F, Cl 및 Br), C1-8알킬, C1-8알콕시, C2-8알켄옥시, C5-8사이클로알콕시 및 페닐옥시로 이루어진 그룹으로부터 선택된 하나 이상의 치환체로 치환된 테트라하이드로피라닐 또는 테트라하이드로푸라닐을 의미한다. 하나 이상의 수소를 갖는 이들 치환체 각각은 할로겐(F, Cl 및 Br)으로 치환된 이러한 수소를 하나 이상 가질 수 있다.The terms "substituted tetrahydropyranyl" and "substituted tetrahydrofuranyl" refer to halo (F, Cl and Br), C 1-8 alkyl, C 1-8 alkoxy, C 2-8 alkenoxy, C 5- Tetrahydropyranyl or tetrahydrofuranyl substituted with one or more substituents selected from the group consisting of 8 cycloalkoxy and phenyloxy. Each of these substituents having one or more hydrogens may have one or more such hydrogens substituted with halogens (F, Cl and Br).
실릴 화합물의 예로, Si(t-Bu)Me2, Si(Ph)Me2, SiEt3및 SiMe3을 들 수 있으나, 이에 한정되는 것은 아니다.Examples of the silyl compound include, but are not limited to, Si (t-Bu) Me 2 , Si (Ph) Me 2 , SiEt 3, and SiMe 3 .
일반적으로, Y는 바람직하게는 H 또는 벤질이며, H가 가장 바람직하다.In general, Y is preferably H or benzyl, with H being most preferred.
환원제가 반응식 GR-I에서 사용된다. 일반적으로, 에스테르를 제거하기 위해 보정된 환원 전위를 갖는 임의의 수소화물이 사용될 수도 있다. 이러한 수소화물의 적합한 예로, (1) R1R2HA1, (2) R1R2R3AlHM 및 (3) R1R2R3BHM을 들 수 있다. 이들 수소화물에 있어서, R1, R2및 R3은 독립적으로 H, C1-8알킬, 헤테로 C1-8알킬, C1-8알콕시 및 헤테로 C1-8알콕시로 이루어진 그룹으로부터 선택된다. 헤테로 C1-8알킬 및 헤테로 C1-8알콕시에서 용어 "헤테로"는 분자 구조의 주쇄에 1 내지 8개의 탄소원자와 1 내지 3개의 산소원자 또는 황원자를 함유하는 분자 구조를 의미한다. 이들 분자 구조의 예로, CH3CH2OCH2CH2-, CH3OCH2CH2OCH2CH2- 및 CH3CH2SCH2CH2-를 들 수 있으나, 이에 한정되는 것은 아니다. M은 Na, Li, K, Ca 및 Zn으로 이루어진 그룹으로부터 선택된다. 일반적으로, 디이소부틸알루미늄 하이드라이드를 사용하는 것이 바람직하다. 일반적으로, GF-I에 대하여 과량의 환원제를 갖는 것이 바람직하다. Y에 의존하는 GF-I에 대하여 약 3 내지 약 4몰의 환원제를 갖는 것이 보다 바람직하다. Y가 H인 경우, GF-I 1몰당 환원제 약 4몰을 갖는 것이 바람직하다. Y가 H가 아닌 경우, GF-I 1몰당 환원제 약 3몰을 갖는 것이 바람직하다.Reducing agents are used in Scheme GR-I. In general, any hydride with a calibrated reduction potential may be used to remove the ester. Suitable examples of such hydrides include (1) R 1 R 2 HA 1 , (2) R 1 R 2 R 3 AlHM and (3) R 1 R 2 R 3 BHM. For these hydrides, R 1 , R 2 and R 3 are independently selected from the group consisting of H, C 1-8 alkyl, hetero C 1-8 alkyl, C 1-8 alkoxy and hetero C 1-8 alkoxy. . The term "hetero" in hetero C 1-8 alkyl and hetero C 1-8 alkoxy means a molecular structure containing 1 to 8 carbon atoms and 1 to 3 oxygen or sulfur atoms in the main chain of the molecular structure. Examples of these molecular structures include, but are not limited to, CH 3 CH 2 OCH 2 CH 2 —, CH 3 OCH 2 CH 2 OCH 2 CH 2 — and CH 3 CH 2 SCH 2 CH 2 —. M is selected from the group consisting of Na, Li, K, Ca and Zn. In general, it is preferable to use diisobutylaluminum hydride. In general, it is desirable to have an excess of reducing agent relative to GF-I. It is more preferred to have about 3 to about 4 moles of reducing agent relative to Y-dependent GF-I. When Y is H, it is preferred to have about 4 moles of reducing agent per mole of GF-I. If Y is not H, it is preferred to have about 3 moles of reducing agent per mole of GF-I.
반응은 비양성자성 용매 중에서 수행된다. 용매는 테트라하이드로푸란,1,4-디옥산, 디클로로메탄, 톨루엔, 디(C1-8알킬) 에테르, C5-8알칸, C3-8사이클로알칸, 1,2-디클로로에탄, 벤젠, 치환된 벤젠, 글림, 디글림 또는 이들의 혼합물로 이루어진 그룹으로부터 선택될 수 있다. 용어 "치환된 벤젠"은 할로(F, Cl 및 Br), C1-3알킬, C1-8알콕시, C2-8알켄옥시, C5-8사이클로알콕시 및 페닐옥시로 이루어진 그룹으로부터 선택된 하나 이상의 치환체로 치환된 벤젠을 의미한다.The reaction is carried out in an aprotic solvent. The solvent is tetrahydrofuran, 1,4-dioxane, dichloromethane, toluene, di (C 1-8 alkyl) ether, C 5-8 alkanes, C 3-8 cycloalkanes, 1,2-dichloroethane, benzene, It may be selected from the group consisting of substituted benzene, glim, diglyme or mixtures thereof. The term "substituted benzene" is one selected from the group consisting of halo (F, Cl and Br), C 1-3 alkyl, C 1-8 alkoxy, C 2-8 alkenoxy, C 5-8 cycloalkoxy and phenyloxy Mean benzene substituted with the above substituents.
반응 조건은 약 -80℃ 내지 약 50℃, 바람직하게는 약 -25℃ 내지 약 25℃의 온도를 포함한다. 일반적으로, 압력은 중요한 것으로 여겨지지는 않으나, 대략 주위 압력 내지 약 50psia의 압력이 사용될 수도 있다. 일반적으로, 사실상 액체 상태의 성분들과의 반응을 수행하는 것이 최선이다.The reaction conditions include a temperature of about -80 ° C to about 50 ° C, preferably about -25 ° C to about 25 ° C. In general, the pressure is not considered important, but a pressure of approximately ambient pressure to about 50 psia may be used. In general, it is best to carry out the reaction with the components in the liquid state.
반응이 사실상 종료된 후, 생성물 GF-II가 반응 혼합물로부터 회수된다. 이는 물, 알콜, 에스테르, 케톤 또는 알데히드(그 예로, 메탄올, 에틸 아세테이트 및 아세톤을 들 수 있으나, 이에 한정되는 것은 아니다)를 첨가하여 반응을 우선 급냉시킴으로써 수행될 수 있다. 이 후, 무기산(그 예로, HCl 및 H2SO4을 들 수 있으나, 이에 한정되는 것은 아니다)을 사용하여 반응 혼합물 성분의 분리를 촉진시킨다. 이 후, 화합물 GF-II를 유기 용매에 추출시킨다. 이러한 유기 용매의 예로, EtOAc 및 메틸렌 클로라이드를 들 수 있으나, 이에 한정되는 것은 아니다.After the reaction is substantially finished, the product GF-II is recovered from the reaction mixture. This can be done by first quenching the reaction by adding water, alcohols, esters, ketones or aldehydes (examples include but are not limited to methanol, ethyl acetate and acetone). Thereafter, inorganic acids (such as, but not limited to, HCl and H 2 SO 4 ) are used to facilitate separation of the reaction mixture components. Thereafter, compound GF-II is extracted in an organic solvent. Examples of such organic solvents include, but are not limited to, EtOAc and methylene chloride.
이들 실시예는 본 발명을 설명하기 위해 제공된다. 이들은 본 발명을 한정하는 것으로 해석됨을 의미하지 않는다.These examples are provided to illustrate the present invention. They do not mean to be construed as limiting the present invention.
천연 생성물 UK-2A(1) 또는 벤질 에테르(2)가 감온 또는 주위 온도에서 염화메틸렌(CH2Cl2) 중의 디이소부틸알루미늄 하이드라이드에 적용되어des-이소부티릴 유도체 3 및 4를 수득한다.Natural product UK-2A (1) or benzyl ether (2) is applied to diisobutylaluminum hydride in methylene chloride (CH 2 Cl 2 ) at reduced temperature or ambient temperature to give des -isobutyryl derivatives 3 and 4 .
(3S,6S,7R,8R)-8-벤질-3-({[3-(벤질옥시)-4-메톡시피리딘-2-일]카보닐}아미노)-6-메틸-4,9-디옥소-1,5-디옥소난-7-일-메틸프로파노에이트(2)의 제조(3S, 6S, 7R, 8R) -8-benzyl-3-({[3- (benzyloxy) -4-methoxypyridin-2-yl] carbonyl} amino) -6-methyl-4,9- Preparation of Dioxo-1,5-dioxonan-7-yl-methylpropanoate (2)
벤질 브로마이드(.233mol, 27.7mL)를 아세톤(1L) 중의 NaI(0.097mol, 14.5g)의 용액에 가한다. 천연 생성물 UK-2A(1)(0.194mol, 100g)을 가한 후, 분말화된 K2CO3(0.388mol, 53g)를 가하고, 혼합물을 밤새 격렬하게 교반한다. 혼합물을 CH2Cl2(500mL)로 희석시키고, H2O(2 ×500mL)로 세척한다. 유기 층을 (MgSO4) 건조시키고, 진공하에 농축시킨다. 재결정화(EtOAc/헥산)는 약 6.5%의 N-벤질화 생성물(LC-MS)을 함유한 회색이 도는 백색 고체(융점 169 내지 170℃)로서 95.5g(79%)의 표제 화합물(2)을 제공한다.1H-NMR 및 MS(M+1 605)가 표제 화합물(2)에 대하여 일치한다. 당해 화합물은 추가의 정제없이 다음 단계에 사용된다. N-벤질화된 부산물은 실리카 겔(용리액으로서의 30% 아세톤/헥산) 플러그를 통한 조 잔류물의 여과에 의한 재결정화 전에 혼합물로부터 제거될 수 있다.Benzyl bromide (.233 mol, 27.7 mL) is added to a solution of NaI (0.097 mol, 14.5 g) in acetone (1 L). The natural product UK-2A (1) (0.194 mol, 100 g) is added, followed by powdered K 2 CO 3 (0.388 mol, 53 g) and the mixture is stirred vigorously overnight. Dilute the mixture with CH 2 Cl 2 (500 mL) and wash with H 2 O (2 × 500 mL). The organic layer is dried (MgSO 4 ) and concentrated in vacuo. Recrystallization (EtOAc / hexane) is a grayish white solid (melting point 169-170 ° C.) containing about 6.5% N-benzylated product (LC-MS), 95.5 g (79%) of the title compound (2). To provide. 1 H-NMR and MS (M + 1 605) are consistent for the title compound (2). The compound is used in the next step without further purification. N-benzylated byproducts may be removed from the mixture prior to recrystallization by filtration of the crude residue through a plug of silica gel (30% acetone / hexane as eluent).
N-[(3S,7R,8R,9S)-7-벤질-8-하이드록시-9-메틸-2,6-디옥소-1,5-디옥소난-3-일]-3-(벤질옥시)-4-메톡시피리딘-2-카복스아미드(4)의 제조N-[(3S, 7R, 8R, 9S) -7-Benzyl-8-hydroxy-9-methyl-2,6-dioxo-1,5-dioxonan-3-yl] -3- (benzyl Preparation of oxy) -4-methoxypyridine-2-carboxamide (4)
디이소부틸알루미늄 하이드라이드(CH2Cl2중의 1.0M, 24.8mmol)를 CH2Cl2(40mL) 중의 표제 화합물(2)(8.27mmol, 5.0g)의 -78℃ 용액에 적가한다. 혼합물을 추가로 15분 동안 교반하고, EtOAc(200mL)로 급냉시키고, 주위 온도로 가온시킨다. 염산(2N, 100mL)을 서서히 가하고, 15분 동안 격렬하게 교반시킨다. 층을 분리시키고, 유기 층을 (MgSO4) 건조시키고, 진공하에 농축시킨다. 잔류물을 크로마토그래피(1% 아세트산/아세톤)에 의해 정제하여 융점 110 내지 114℃의 유리같은 백색 고체 1.54g(35%)을 수득한다.1H-NMR 및 MS(M+1 535)가 목적하는 생성물과 일치한다.Diisobutyl aluminum hydride (CH 2 Cl 2 in 1.0M, 24.8mmol) was added dropwise to the -78 ℃ solution of the title compound (2) (8.27mmol, 5.0g) in CH 2 Cl 2 (40mL). The mixture is stirred for an additional 15 minutes, quenched with EtOAc (200 mL) and warmed to ambient temperature. Hydrochloric acid (2N, 100 mL) is added slowly and vigorously stirred for 15 minutes. The layers are separated and the organic layer is dried (MgSO 4 ) and concentrated in vacuo. The residue is purified by chromatography (1% acetic acid / acetone) to yield 1.54 g (35%) of a glassy white solid with a melting point of 110 to 114 ° C. 1 H-NMR and MS (M + 1 535) are consistent with the desired product.
N-[(3S,7R,8R,9S)-7-벤질-8-하이드록시-9-메틸-2,6-디옥소-1,5-디옥소난-3-일]-3-하이드록시-4-메톡시피리딘-2-카복스아미드(3)의 제조N-[(3S, 7R, 8R, 9S) -7-benzyl-8-hydroxy-9-methyl-2,6-dioxo-1,5-dioxonan-3-yl] -3-hydroxy Preparation of -4-methoxypyridine-2-carboxamide (3)
디이소부틸알루미늄 하이드라이드(CH2Cl2중의 1.0M, 23.3mmol)를 CH2Cl2(60mL) 중의 천연 생성물 UK-2A(1)(5.8mmol, 3.0g)의 20℃ 용액에 적가한다. 혼합물을 추가로 15분 동안 교반하고, EtOAc(10mL)로 급냉시킨다. 염산(2N,100mL)을 서서히 가하고, 15분 동안 격렬하게 교반시킨다. 층을 분리시키고, 유기 층을 (MgSO4) 건조시키고, 진공하에 농축시켜 거품같은 밝은 황색 고체로서 표제 화합물(3) 1.82g(70%)을 수득한다.1H-NMR(300MHz, CDCl3): δ 11.82(s, 1H), 8.63(d, J = 8.2Hz, 1H), 8.01(d, J = 5.2Hz, 1H), 7.32-7.20(m, 5H), 6.89(d, J = 5.2Hz), 5.35(m, 1H), 5.16(m, 1H), 4.86(m, 1H), 3.96(s, 3H), 3.76(t, J = 9.4Hz, 1H), 3.62(m, 1H), 3.25(m, 1H), 3.02(m, 1H), 2.77(m, 1H), 1.51(d, J = 6.3Hz, 3H);13C NMR(MHz, CDCl3): δ 173.2, 170.2, 169.4, 155.8, 149.2, 141.1, 138.8, 130.3, 129.2, 129.0, 127.0, 110.1, 77.6, 77.2, 65.4, 56.5, 54.4, 50.3, 35.4, 18.7 ppm; IR (KBr 펠릿): 3370 (br), 2966, 1751, 1654, 1529, 1453, 1263, 1045, 801 cm-1; 추출물 질량: C22H24N2O8[M]+에 대한 m/z 이론치 = 444.1533, 실측치 444.1513.Diisobutylaluminum hydride (1.0 M in CH 2 Cl 2 , 23.3 mmol) is added dropwise to a 20 ° C. solution of the natural product UK-2A (1) (5.8 mmol, 3.0 g) in CH 2 Cl 2 (60 mL). The mixture is stirred for an additional 15 minutes and quenched with EtOAc (10 mL). Hydrochloric acid (2N, 100 mL) was added slowly and vigorously stirred for 15 minutes. The layers are separated and the organic layer is dried (MgSO 4 ) and concentrated in vacuo to yield 1.82 g (70%) of the title compound (3) as a pale light yellow solid. 1 H-NMR (300 MHz, CDCl 3 ): δ 11.82 (s, 1H), 8.63 (d, J = 8.2 Hz, 1H), 8.01 (d, J = 5.2 Hz, 1H), 7.32-7.20 (m, 5H ), 6.89 (d, J = 5.2 Hz), 5.35 (m, 1H), 5.16 (m, 1H), 4.86 (m, 1H), 3.96 (s, 3H), 3.76 (t, J = 9.4 Hz, 1H ), 3.62 (m, 1H), 3.25 (m, 1H), 3.02 (m, 1H), 2.77 (m, 1H), 1.51 (d, J = 6.3 Hz, 3H); 13 C NMR (MHz, CDCl 3 ): δ 173.2, 170.2, 169.4, 155.8, 149.2, 141.1, 138.8, 130.3, 129.2, 129.0, 127.0, 110.1, 77.6, 77.2, 65.4, 56.5, 54.4, 50.3, 35.4, 18.7 ppm; IR (KBr pellet): 3370 (br), 2966, 1751, 1654, 1529, 1453, 1263, 1045, 801 cm −1 ; Extract mass: m / z theory for C 22 H 24 N 2 O 8 [M] + = 444.1533. Found 444.1513.
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| RU2014149186A (en) | 2012-05-07 | 2016-06-27 | ДАУ АГРОСАЙЕНСИЗ ЭлЭлСи | MACROCYCLIC PICOLINAMIDES AS FUNGICIDES |
| CN104284589B (en) | 2012-05-07 | 2018-05-01 | 陶氏益农公司 | Purposes of the preceding fungicide of UK-2A in banana secret note leaf spot is prevented |
| WO2013169664A2 (en) * | 2012-05-07 | 2013-11-14 | Dow Agrosciences Llc | Macrocycle picolinamides as fungicides |
| AU2013370491B2 (en) | 2012-12-28 | 2016-10-06 | Corteva Agriscience Llc | Synergistic fungicidal mixtures for fungal control in cereals |
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| WO2015100182A1 (en) | 2013-12-26 | 2015-07-02 | Dow Agrosciences Llc | Use of macrocyclic picolinamides as fungicides |
| EP3099170A4 (en) | 2013-12-26 | 2017-06-21 | Dow AgroSciences LLC | Use of macrocyclic picolinamides as fungicides |
| NZ720907A (en) | 2013-12-31 | 2017-05-26 | Dow Agrosciences Llc | Synergistic fungicidal mixtures for fungal control in cereals |
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| MX2016017124A (en) | 2014-07-08 | 2017-05-10 | Dow Agrosciences Llc | Process for the preparation of 3-hydroxypicolinic acids. |
| CN106470983A (en) | 2014-07-08 | 2017-03-01 | 美国陶氏益农公司 | Big ring picolinamide as antifungal |
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| HUP0600298A2 (en) | 2006-07-28 |
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